Flexible endoscopy is a class of minimally-invasive procedures wherein a flexible device is maneuvered through the body's existing hollow organs (e.g., tracheobronchial airway tree, colon, sinuses) in order to perform diagnosis or deliver treatment.1,2 Endoscopy reduces and often eliminates the need for incisions, thereby reducing patient risk and recovery time. Flexible endoscopy is therefore preferable to more invasive surgeries, which typically require an incision large enough for the physician to directly view and manipulate the target operating region.
Endoscopy may be used, for example, in the chest, where routine and relatively low-risk bronchoscopic biopsies can replace transthoracic biopsies that carry the risk of pneumothorax.1,3,4 Similarly, flexible endoscopy may be used in the heart to facilitate insertion of cardiac pacemaker leads,5 in the nasal and sinus passages to assist in diagnoses,6 and in the colon to detect and treat colonic polyps.7 
The typical workflow of an endoscopic procedure consists of two phases: Phase I, Pre-operative planning; and Phase II, Endoscopy. During Phase I, a three-dimensional (3D) volumetric image—typically acquired by a multi-detector computed tomography (MDCT) or magnetic resonance imaging (MRI) scanner—is acquired for the anatomy of interest.8-10 Regions of interest (ROIs), such as lymph nodes, suspicious nodules, polyps, etc., are defined by a physician examining a series of 2D transverse slices of this 3D image. During this phase, the endoscopist also plans a route to each ROI, choosing the approach that allows best access for diagnosis and treatment options.11 
In standard practice, the MDCT scan is displayed on a computer monitor or x-ray film view panel as a series of transverse-plane slices through the chest. Route planning in this case consists of determining a path from the trachea to a location within the tracheobronchial tree from which the ROI is accessible. In standard practice, this step requires the bronchoscopist to mentally reconstruct the anatomy in 3D to determine the best approach to the ROI. It has been shown, however, that the path is often chosen incorrectly using this approach and that physicians have difficulty in identifying airways in CT slices as early as the second generation.12,13 
In Phase II, the physician performs the endoscopic procedure. Central to this procedure is the task of navigating the endoscope tip to the previously-defined ROIs, relying on both the live endoscopic video feed as well as the analysis of the 3D image performed in Phase I. This task is difficult for several reasons: 1) the ROIs can lie beyond the walls of the hollow organ and are not visible in the endoscopic video; 2) the endoscopic video is markedly different from the 3D radiologic images in which these ROIs are defined; and 3) endoscopic views from different locations within the organ can be visually indistinguishable.
In bronchoscopy, these difficulties are exacerbated by the complexity of the tracheobronchial airway tree in which the bronchoscope operates. These effects result in navigation errors and are known to contribute to large variations in skill level between different physicians.14,15 Such errors may also result in missed diagnoses, necessitating invasive and potentially fatal follow-up procedures.3,4 Previously, image-based and electromagnetic (E/M) guidance techniques have been proposed to aid physicians both in navigation to ROIs and in improving the biopsy accuracy of ROIs.
E/M guidance techniques generate an E/M field around the patient, and locate the bronchoscope using an E/M sensor inserted through the instrument channel of the bronchoscope.16-21 These techniques require special hardware that adds to the cost of each procedure and limits the type of bronchoscope that can be used. Because the E/M probe occupies the bronchoscope's instrument channel, these techniques are not suitable for the smaller channels present on small-diameter endoscopes designed for pediatric or peripheral lung procedures. Furthermore, the E/M probe must be removed from the channel before performing critical procedural steps (e.g., performing biopsy), leaving the physician without location information. In addition, E/M registration can only locate the bronchoscope relative to an external field. It is therefore susceptible to localization errors in the face of patient breathing motion, shifting of the patient during the procedure or different body position between the 3D scan and the procedure, although recent research has begun to address these problems.19,21,22 
Image-based guidance techniques rely on volumetric image processing in order to serve as a guidance aid for the physician. Virtual bronchoscopic (VB) guidance techniques present the physician with surface or volumetric renderings of the tracheobronchial airway tree that mimic the appearance of real bronchoscopic (RB) video.23-27 These techniques rely on a technician to move the virtual bronchoscope in tandem with the physician moving the real bronchoscope, in order to provide the physician with more awareness of location within the airways and with respect to the ROIs. While VB guidance has shown promise to improve performance of bronchoscopic procedures, the VB world and the RB world are not directly linked, leaving the physician to make the final inference. In contrast, virtual-to-real (V-R) registration/tracking methods provide an automated link between the volumetric-image-based VB source and the RB video source.28-35 
This link reduces user intervention and allows fusion of data between the two sources. However, it has previously been computationally intensive, limiting its use to single-frame or buffered-video applications, and requiring the physician to wait several seconds for each registration result.